Beadle and Tatum's key experiments involved exposing the bread mouldNeurospora crassa to x-rays, causing mutations. In a series of experiments, they showed that these mutations caused changes in specific enzymes involved in pathways making proteins. They proposed a direct link between genes and enzymatic reactions, known as the "one gene, one enzyme" hypothesis.

In 1935 Beadle visited Paris for six months to work with Boris Ephrussi at the Institut de Biologie physico-chimique. Together they began the study of the development of eye pigment in Drosophila which later led to the work on the biochemistry of the genetics of the fungusNeurospora.

In 1937 Beadle was appointed Professor of Biology (Genetics) at Stanford University and there he remained for nine years, working for most of this period in collaboration with Tatum.

In 1946 he returned to the California Institute of Technology as Professor of Biology and Chairman of the Division of Biology. Here he remained until January 1961 when he was elected Chancellor of the University of Chicago and, in the autumn of the same year, President of this University.

In 1977, work by the Sharp and Roberts labs showed that genes of higher organisms are "split" or present in several distinct segments along the DNA molecule.[3][4]

The coding regions of the gene are separated by non-coding DNA that is not involved in protein expression. The non-coding regions, the introns, are cut from the precursor mRNAs in a process called "splicing". The split gene structure was found to be common to most eukaryotic genes. For this reason, one gene–one enzyme does not hold in the simple way put forward by Beadle and Tatum. This is because

It may take more than one gene to build a protein, and

Many different genes can be made from a smaller set of genes (see antibody).